Drug residence time

Prolonged presence of the drug at the site of injection is the aim of liposome encapsulation of drugs, which are injected in the vitreous body. Both amphotericin and gentamicin in liposome formulations were cleared from the injection site significantly more slowly than the free drug residence times depended on liposome size and, in some cases, on bilayer composition (Tremblay et al., 1985 Barza et al., 1985, 1987 Fishman et al., 1986). 

PR Byron. Prediction of drug residence times in regions of the human respiratory tract following aerosol inhalation. J Pharm Sci 75 433-438, 1986. 

Chitosan has been shown to increase precorneal drug residence times. The cationic chitosan slows tear drainage by increasing viscosity and by mucoadhesion with the negatively charged mucin. Up to a threefold increase of the corneal residence time has been achieved by the addition of chitosan to topical vehicles [5]. Carbomer gels at 0.3% have also been shown to be effective in prolonging the tear film break-up time [6]. Hyaluronic acid has been reported to... 

A popular approach to improve ocular drag bioavailability is to incorporate soluble polymers into an aqueous solution to extend the drug residence time in the cul-de-sac. It is reasoned that the solution viscosity would be increased and hence solution drainage would be reduced. The more commonly used viscolyzing agents include PVA and derivatives of cellulose. Cellulosic polymers, such as methylcellulose, hydroxyethylcellulose (HEC), hydroxypropyl-methylcellulose (HPMC) and hydroxypropylcellulose (HPC), are widely used as viscolyzers showing Newtonian properties. They have common properties ... 

Betaxolol is suppUed as a sterile suspension of 0.25% betaxolol HCl (Betoptic-S). The suspension is a unique formulation containing a polyacrylic acid polymer (carbomer 934P) and a cationic exchange resin, which is beUeved to increase the drug residence time in the eye (see Chapter 2). This product is the racemic compoimd, preserved with 0.01% BAC, and approved for twice-daily use. 

Drug entrapment in liposomes has been most extensively investigated, and evidence has been presented both in experimental animals and in humans that the drug residence time in the lung can be substantially extended [123— 129,131],... 

The use of inhalation therapy has been applied mainly to the treatment of asthma and bronchitis. There is an increasing awareness that current treatment is inadequate and that the incidence of asthma is on the rise [31]. Indeed, it has been shown that an apparent increase in the prevalence of asthma at childhood has occurred in recent years [32]. Of particular recent interest is the structure-activity relationships associated with drug residence times in the respiratory tract. 

It is now common knowledge that the topical controlled delivery of ophthalmic drugs improves their ocular bioavailability with respect to traditional eye drops, by decreasing the rate of drug elimination from the precorneal area. When the controlled delivery is realized via an erodible insert, the drug residence time in the precorneal area, and thereby, the bioavailability will be maximized if the drug release is controlled exclusively by insert erosion, since any parallel release mechanism increases the release rate, and thereby, the dose fraction cleared from the precorneal area by tear fluid draining. 

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